Abstract—We studied the effect of chronic neuropathic pain on the state of microglia and neurogenesis in the hippocampus in old mice. Neuropathic pain was induced by imposing three ligatures on the sciatic nerve of the right hind limb of animals. Testing behavior showed the presence of impaired working memory and locomotor activity in animals with neuropathic pain both in 1 week and 3 weeks after surgery. Behavioral disorders were accompanied by a decrease in hippocampal neurogenesis, as well as an increase in the expression of microglial markers Iba-1 and CD86 in the hippocampus of animals with a ligated sciatic nerve. In addition, the induction of neuropathic pain led to a change in the expression of astroglial markers S100β and GFAP in the hippocampus. The findings suggest that behavioral changes in neuropathic pain are accompanied by changes in the activity of microglia and astroglia, which leads to disruption of neurogenesis and a decrease in cognitive functions.
Similar content being viewed by others
REFERENCES
Merskey, H. and Bogduk, N., Pain Terms: A Current List with Definitions and Notes on Usage: Classification of Chronic Pain, 2nd ed., Seattle: IASP Task Force on Taxonomy, 1994.
Finnerup, N.B., Sindrup, S.H., and Jensen, T.S., Fundamental & Clinical Pharmacology, 2007, vol. 21, no. 2, pp. 129–136.
Liu, M.G. and Chen, J., Neuroscience Bulletin, 2009, vol. 25, no. 5, p. 237.
McEwen, B.S., Ann. N. Y. Acad. Sci., 2001, vol. 933, no. 1, pp. 265–277.
Dimitrov, E.L., Tsuda, M.C., Cameron, H.A., and Usdin, T.B.J., Neurosci., 2014, vol. 34, no. 37, pp. 12304–12312.
Baron, R., Binder, A., and Wasner, G., The Lancet Neurology, 2010, vol. 9, no. 8, pp. 807–819.
Maier, C., Baron, R., Tölle, T.R., Binder, A., Birbaumer, N., Birklein, F., Gierthmühlen, J., Flor, H., Geber, C., Huge, V., and Krumova, E.K., Pain, 2010, vol. 150, no. 3, pp. 439–450.
Fillingim, R.B., King, C.D., Ribeiro-Dasilva, M.C., Rahim-Williams, B., and Riley, J.L., 3rd., J., Pain, 2009, vol. 10, no. 5, pp. 447–485.
Leite-Almeida, H., Almeida-Torres, L., Mesquita, A.R., Pertovaara, A., Sousa, N., Cerqueira, J.J., and Almeida, A., Pain, 2009, vol. 144, nos. 1–2, pp. 57–65.
Jones, M.R., Ehrhardt, K.P., Ripoll, J.G., Sharma, B., Padnos, I.W., Kaye, R.J., and Kaye, A.D., Curr. Pain Headache Rep., vol. 20, no. 4, p. 23.
Tyrtyshnaia, A.A., Manzhulo, I.V., Sultanov, R.M., and Ermolenko, E.V., Acta Histochem., 2017, vol. 119, no. 8, pp. 812–821.
Bennett, G.J. and Xie, Y.K., Pain, vol. 198833, no. 1, pp. 87–107.
Allen, J.W. and Yaksh, T.L., Pain Research: Methods and Protocols, 2004, pp. 11–23.
Knowles, J.K., Simmons, D.A., Nguyen, T.V.V., Vander Griend, L., Xie, Y., Zhang, H., Yang, T., Pollak, J., Chang, T., Arancio, O., and Buckwalter, M.S., Neurobiol. Aging, 2013, vol. 34, no. 8, pp. 2052–2063.
Rusanescu, G. and Mao, J.J., Cell. Mol. Med., 2017, vol. 21, no. 2, pp. 299–314.
Seifert, F. and Maihofner, C., Curr. Opin. Anesthesiol., 2011, vol. 24, no. 5, pp. 515–523.
Deng, W., Aimone, J.B., and Gage, F.H., Nat. Rev. Neurosci., 2010, vol. 11, no. 5, p. 339.
Sahay, A. and Hen, R., Nat. Neurosci., 2007, vol. 10, no. 9, p. 1110–1115.
Revest, J.M., Dupret, D., Koehl, M., Funk-Reiter, C., Grosjean, N., Piazza, P.V., and Abrous, D.N., Mol. Psychiatry, 2009, vol. 14, no. 10, p. 959–967.
Dranovsky, A. and Hen, R., Biol. Psychiatry, 2006, vol. 59, no. 12, pp. 1136–1143.
Saxe, M.D., Battaglia, F., Wang, J.W., Malleret, G., David, D.J., Monckton, J.E., Garcia, A.D.R., Sofroniew, M.V., Kandel, E.R., Santarelli, L., and Hen, R., Proc. Natl. Acad. Sci. U.S.A., 2006, vol. 103, no. 46, pp. 17501–17506.
Van Praag, H., Shubert, T., Zhao, C., and Gage, F.H.J., Neurosci., 2005, vol. 25, no. 38, pp. 8680–8685.
Egeland, M., Zunszain, P.A., and Pariante, C.M., Nat. Rev. Neurosci., 2015, vol. 16, no. 4, p. 189–200.
Ekdahl, C.T., Claasen, J.H., Bonde, S., Kokaia, Z., and Lindvall, O., Proc. Natl. Acad. Sci. U.S.A., 2003, vol. 100, no. 23, pp. 13632–13637.
Butovsky, O., Kunis, G., Koronyo-Hamaoui, M., and Schwartz, M., Eur. J. Neurosci., 2007, vol. 26, no. 2, pp. 413–416.
Roughton, K., et al., Dev. Neurosci., 2013, vol. 35, no. 5, pp. 406–415.
Kuzumaki, N., Ikegami, D., Imai, S., Narita, M., Tamura, R., Yajima, M., Suzuki, A., Miyashita, K., Niikura, K., Takeshima, H., and Ando, T., Synapse, 2010, vol. 64, no. 9, pp. 721–728.
Montgomery, S.L. and Bowers, W.J.J., Neuroimmune Pharmacol., 2012, vol. 7, no. 1, pp. 42–59.
Butovsky, O., Ziv, Y., Schwartz, A., Landa, G., Talpalar, A.E., Pluchino, S., Martino, G., and Schwartz, M., Mol. Cell. Neurosci., 2006, vol. 31, no. 1, pp. 149–160.
Nikolakopoulou, A.M., Dutta, R., Chen, Z., Miller, R.H., and Trapp, B.D., Proc. Natl. Acad. Sci. U.S.A., 2013, vol. 110, no. 21, pp. 8714–8719.
Perea, G., Navarrete, M., and Araque, A., Trends Neurosci., 2009, vol. 32, no. 8, pp. 421–431.
Figley, C.R. and Stroman, P.W., Eur. J. Neurosci., 2011, vol. 33, no. 4, pp. 577–588.
Gabriel, S., Njunting, M., Pomper, J.K., Merschhemke, M., Sanabria, E.R., Eilers, A., Kivi, A., Zeller, M., Meencke, H.J., Cavalheiro, E.A., Heinemann, U., and Lehmann, T.N., J. Neurosci., 2004, vol. 24, no. 46, pp. 10416–10430.
Ishibashi, T., Dakin, K.A., Stevens, B., Lee, P.R., Kozlov, S.V., Stewart, C.L., and Fields, R.D., Neuron, 2006, vol. 49, no. 6, pp. 823–832.
Han, X., Chen, M., Wang, F., Windrem, M., Wang, S., Shanz, S., Xu, Q., Oberheim, N.A., and Bekar, L., Cell Stem Cell, 2013, vol. 12, no. 3, pp. 342–353.
Zhao, X., Ahram, A., Berman, R.F., Muizelaar, J.P., and Lyeth, B.G., Glia, 2003, vol. 44, no. 2, pp. 140–152.
Ouyang, Y.B., Voloboueva, L.A., Xu, L.J., and Giffard, R.G., J. Neuroscience, 2007, vol. 27, no. 16, pp. 4253–4260.
Gosselin, R.D., Gibney, S., O’Malley, D., Dinan, T.G., and Cryan, J.F., Neuroscience, 2009, vol. 159, no. 2, pp. 915–925.
Bridges, N., Slais, K., and Syková, E., Acta Neurobiol. Exp., vol. 68, no. 2, p. 131.
Farina, C., Aloisi, F., and Meinl, E., Trends Immunol., 2007, vol. 28, no. 3, pp. 138–145.
Raponi, E., Agenes, F., Delphin, C., Assard, N., Baudier, J., Legraverend, C., and Deloulme, J.C., Glia, 2007, vol. 55, no. 2, pp. 165–177.
Sato, K., Glia, 2015, vol. 63, no. 8, pp. 1394–1405.
Funding
This study was funded by Russian Foundation for Basic research (grant no. 18-34-00120 mol_а).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest. The authors declare that they have no conflict of interest.
Ethical approval. All procedures were approved by the Animal Ethics Committee at National Scientific Center of Marine Biology Far Eastern Branch, Russian Academy of Sciences, according to the Laboratory Animal Welfare guidelines.
Rights and permissions
About this article
Cite this article
Tyrtyshnaia, A.A., Manzhulo, I.V., Konovalova, S.P. et al. The Effects of Neuropathic Pain on the State of Glial Cells and Hippocampal Neurogenesis in Old Animals. Neurochem. J. 13, 355–366 (2019). https://doi.org/10.1134/S1819712419030140
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1819712419030140